Enterovirus type 71 (EV71) has caused several major outbreaks. It usually infects young children and causes hand, foot and mouth disease. It also has the potential to cause severe neurological diseases. Until now, there is no antiviral agent known to be effective in treating EV71 infection.
EV71 was first isolated in California, USA in 1969 (Wang, J. R. et al., Change of Major Genotype of Enterovirus 71 in Outbreaks of Hand-Foot-and-Mouth Disease in Taiwan between 1998 and 2000. Journal of Clinical Microbiology 40, 10-15, 2002). It has become an important clinical issue around Asia-Pacific region (McMinn et al., Phylogenetic Analysis of Enterovirus 71 Strains Isolated during Linked Epidemics in Malaysia, Singapore, and Western Australia. Journal of Virology 75, 7732-7738, 2001). EV71 usually infects young children with age of 3 years or younger. It may cause rashes, severe neurological disease and hand, foot and mouth disease (HFMD) (Repass et al., Hand, foot, and mouth disease: identifying and managing an acute viral syndrome. Cleveland Clinic journal of medicine 81, 537-543, 2014). In Taiwan, many big outbreaks with fatal cases have been reported since 1998. Hence, it is important to develop vaccines for prevention and effective drugs for treatment.
Various EV71 vaccine candidates are being researched in animal models, including live-attenuated virus vaccine, recombinant VP1 vaccine, synthetic peptide vaccine and virus-like particle vaccine (Kung et al., Update on the development of enterovirus 71 vaccines. Expert Opinion on Biological Therapy 14, 1455-1464, 2014). Recently, a phase III clinical trial of an EV71 vaccine has been completed in China, and two phase I clinical trials have been completed in Taiwan and Singapore respectively. They are all inactivated whole-virus alum-adjuvant vaccines which separately use isolated C4 genotype virus as vaccine strain (Liang and Wang, EV71 vaccine, an invaluable gift for children. Clin Trans Immunol 3, e28, 2014). Their protective efficacies were over 90% on EV71-associated HFMD and over 80% on other EV71-associated diseases.
Accordingly, it is desirable to develop a novel therapeutics for EV17 infections.